Abstract Details

Title Association of Specific “Critical” Demyelinating Lesions and Motor Impairment in Progressive Multiple Sclerosis: A Prospective Study

Topic Multiple Sclerosis

Presentation(s) S46 - MS Therapeutics and Clinical Decision Making (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Background “Critical” demyelinating lesions are anatomically associated with progressive motor impairment in highly selected cohorts with demyelinating disease.

Objective We aimed to determine the frequency of “critical” lesions in individuals with progressive Multiple Sclerosis at a tertiary MS clinic.

Design/Methods Prospective, consecutively enrolled, observational cohort study of established and newly evaluated people with progressive MS at Mayo Clinic from July 1, 2021, to March 31, 2022. Comprehensive neurological examination was performed by subspecialty MS experts and clinical information and brain and spinal cord MRIs were reviewed. Progressive MS was determined to be predominantly progressive motor, cognitive, cerebellar or sensory impairment. MRI assessment was compared to clinical progressive motor impairment to determine those with: 1) one or two “tandem” “critical” demyelinating lesions with anatomic association to progressive motor impairment, often with lateral axial spinal cord distribution and focal lesion associated atrophy, 2) demyelinating lesion burden too large to identify specific lesion-associated motor progression

Results

196 consecutive people with progressive MS (126, 64.3% SPMS, 70, 35.7% PPMS) were included (128, 65.3% established in the MS clinic and 68, 34.7% newly evaluated). 181, 92.3% people had progressive motor impairment as their presentation, 13, 6.2% ataxic and 2, 1% sensory. Among those with progressive motor impairment, 149, 76% had lesion burden too large to determine specific, lesion-associated motor progression. A specific focal “critical” lesion anatomically associated with progressive motor impairment was found in 47 (24%) (38 [19.4%] with one “critical” and 9 [4.6%] two “tandem” “critical” lesions). “Critical” demyelinating lesions were most commonly found within the lateral column of the cervical spinal cord.

Conclusions A statistically significant number of individuals (24%) with progressive MS have specific “critical” demyelinating lesions anatomically associated with progressive motor impairment. “Critical” demyelinating lesions are potential prognostic and therapeutic targets for progressive motor impairment in some people with MS.

Authors/Disclosures
Rowaid Ahmad, MBBS PRESENTER	Dr. Ahmad has nothing to disclose.
Caitlin Tarlton, MD (NSHA)	Dr. Tarlton has nothing to disclose.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from Viela Bio. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
W. O. Tobin, PhD, MBBCh, BAO, FAAN (Mayo Clinic)	The institution of Dr. Tobin has received research support from Mallinckrodt. Dr. Tobin has received publishing royalties from a publication relating to health care. Dr. Tobin has received personal compensation in the range of $500-$4,999 for serving as a Speaker with NeurologyLive.
Michel Toledano, MD (Mayo Clinic)	Dr. Toledano has nothing to disclose.
Sean J. Pittock, MD (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Claudia F. Lucchinetti, MD, FAAN (University of De Medical School, Health Learning Blg)	The institution of Dr. Lucchinetti has received research support from Biogen Idec. The institution of Dr. Lucchinetti has received research support from NIH/NINDS. The institution of Dr. Lucchinetti has received research support from National Institute of Neurological Disorders and Stroke . The institution of Dr. Lucchinetti has received research support from National Multiple Sclerosis Society. The institution of Dr. Lucchinetti has received research support from National Center for Advancing Translational Sciences. Dr. Lucchinetti has received intellectual property interests from a discovery or technology relating to health care. Dr. Lucchinetti has a non-compensated relationship as a Member with National Institute of Neurological Disorders that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Board of Directors, Association of University Professors of Neurology that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Trustees that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Governors that is relevant to AAN interests or activities.
Brian G. Weinshenker, MD, FAAN (University of Virginia Health System)	Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $0-$499 for serving as a Consultant for CALIBR. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. The institution of Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a speaker at internal meeting and symposium with Horizon.
Orhun H. Kantarci, MD	Dr. Kantarci has nothing to disclose.
Mark Keegan, MD, FAAN (Mayo Clinic)	Dr. Keegan has received publishing royalties from a publication relating to health care.